The induction of immunological tolerance in T cells can possibly occur prior to their entry into the thymus, during thymic differentiation or after the cells have emigrated from the thymus. Experimental systems have been constructed to investigate the susceptibility of T cells or their precursors to tolerance induction during the various phases of their differentiation. The basic model consists of murine thymus engrafted radiation bone marrow chimeras in which cell surface alloantigens can, in theory, be specifically localized in the extra-thymic or intra-thymic differentiation environments. Thus far, the induction of tolerance to two distinct cell surface alloantigen systems has been studied; they are those encoded by the MHC and the Mls loci. The results demonstrate that tolerance to MHC encoded alloantigens can occur both pre-thymically and intra-thymically and that tolerance to Mls encoded determinants can occur intra-thymically and post-thymically, but not pre-thymically. These results demonstrate that tolerance to various cell surface alloantigens may occur at different stages of T cell differentiation.